The present disclosure relates in general to assessing and visualizing biological pathways. More specifically, the present disclosure relates to systems and methodologies for assessing a relevance of a biological pathway to a particular disease state, and for simplifying visualization of the biological pathway that was assessed as relevant to the particular disease state.
Numerous genome-wide association studies of diseases have suggested thousands of causal and correlative links between DNA sequence variants and specific disease phenotypes. These suspected or validated variants often reside within genes and open reading frames that can be mapped to biological pathways. A biological pathway is an ordered set of interactions between intracellular molecules having collective activity that impacts cellular function, for example, by controlling metabolite synthesis or by regulating the expression of sets of genes.
A diagram depicting exemplary biological pathways of a typical cell is shown in FIG. 1. As shown, cells are constantly receiving cues from both inside and outside the body, which are prompted by stimuli such as injury, infection, stress or even food. To react and adjust to these cues, cells send and receive signals through biological pathways. Some of the most common biological pathways are involved in metabolism, the regulation of genes and the transmission of signals. The majority of cellular pathways can be classified as signaling pathways (impacting gene expression) or metabolic pathways (regulating biochemical synthesis). While some molecules, like oxygen, can easily travel through the cell membrane, signals go through structures on the cell surface, called receptors. After interacting with a receptor, the signal travels through the cell where its message is transmitted and changed by specialized proteins or other molecules residing in the cell. Signals can be involved in chemical reactions, triggering the assembly of new molecules, inducing cell movement, turning genes on or off, or even changing the shape of a cell. A given gene can reside in multiple pathways and can alter the activity of multiple downstream pathways. Therefore, a function-altering variant within a single gene can impact more than one pathway. Pathways play a key role in the advancement of our understanding of biological processes in the cell.
Pathway information is available through a large number of databases ranging from high quality databases created by professional curators to massive databases covering a vast number of pathways created through natural language processing (NLP) and text mining of abstracts. For example, some pathway databases provide detailed metabolic pathways, while other pathway databases provide detailed signaling pathways. Because of the differences in size, quality and or property, it can be a challenge to select a pathway database, and further to identify the pathways with the selected pathway database, that are aligned with the user's purpose.
A typical pathway database includes the capability to visualize pathways through pathway diagrams, which combine metabolic, genetic and signaling networks based on the literature. Software applications are available that allow for the production, editing and analysis of pathway diagrams. A pathway diagram is usually represented via a directed graph. A directed graph (or digraph, or directed network) is a graph or a set of objects called vertices or nodes that are connected together, wherein all the edges are directed from one vertex to another. The ability to visualize pathway diagrams plays a fundamental role in interpreting and understanding biological processes.